Moderate to severe pain following surgery is common, even after surgeries thought of as minor. Opioids are the mainstay for acute postoperative pain care despite their known side effects and related adverse events. Most research to date has focused on the anesthetic and surgical factors associated with higher acute pain, thereby largely ignoring the inter-patient variability in pain sensitivity. As such, pharmacological adjuncts to opioids and regional anesthetics have been broadly applied in an all or none fashion rather than personalized based on patient characteristics. There is a growing appreciation of the importance of altered central nervous system (CNS) processing of pain and other symptoms in chronic pain states. The widespread body pain, hyperalgesia and comorbid symptomatology of centralized pain states has been best studied in fibromyalgia. Rather than being present or absent, fibromyalgia symptoms occur on a continuum that has been termed fibromyalgianess and can serve as a crude surrogate of the degree of centralization. Opioids are thought to be less effective in centralized pain patients. Our primary hypothesis is that although peripheral nociceptive input is important in the acute pain response, some patients possess varying degrees of CNS amplification (higher fibromyalgianess) that plays an equally or even more prominent role in the expression of pain and opioid consumption. Thus, we hypothesize that the patients with pain that is more centralized in that the degree of pain centralization as measured on a simple self-report measure strongly predicts acute opioid pain responsiveness by providing a surrogate measure of endogenous opioid tone. To test our hypothesis, we will conduct a prospective assessment of pain, opioid consumption and adverse acute postoperative period in patients undergoing total knee arthroplasty (n=200). These data will be used to assess whether fibromyalgianess predicts higher acute pain, more opioid consumption, and a lesser response of pain for the opioids administered. To assess the mechanistic underpinnings of these clinical findings, we will conduct preoperative functional imaging (fMRI and PET scanning) in 60 of the 200 knee arthroplasty patients across the continuum of fibromyalgianess to determine preoperative opioid tone and previously described brain imaging findings of hyperalgesia. The opioid consumption and pain reports will then be analyzed with the brain imaging findings. Consistent with our long term goal of personalized pain medicine, the proposed research could have a major impact on clinical practice because a subset of individuals could be easily identified who would be strong candidates for non- or reduced opioid acute analgesic regimens.